How can I be sure that the patient has gallstones/acute cholecystitis?

Biliary colic is caused by obstruction of the outflow of bile from the contracting gallbladder in response to vagal stimulation and the hormone cholecystokinin (CCK). Acute cholecystitis is caused by persistent obstruction of the cystic duct by a gallstone. As flowing bile is aseptic but not sterile, this obstruction leads to infection of the gallbladder, typically with enteric organisms.

Risk factors for gallstones include blood dyscrasias (pigment stones), being female, multiple pregnancies, obesity, age more than 40 years, somatostatin analog therapy, TPN-dependence, previous ileal resection, Western diet, and rapid weight loss or prolonged fasting. There are also underlying genetic factors; the prevalence of gallstones nears 100% in certain Native American tribes.

Symptoms consistent with acute cholecystitis include epigastric or right upper quadrant pain, often referred into the right flank or to the right shoulder and scapula (Kehr's sign), nausea and/or vomiting, and anorexia. These symptoms classically occur 30 min to 2 hr following a meal that is typically but not necessarily high in fat content.

As opposed to symptomatic cholelithiasis, with acute cholecystitis the pain should persistent greater than 6 hrs. The presence of fever higher than 101.5 F or 38.8 C defines acute cholecystitis from symptomatic cholelithiasis, but the absence of fever does not exclude the diagnosis of acute cholecystitis.

Physical findings should include tenderness to palpation in the epigastrium and right upper quadrant. A palpable mass may be appreciated in patients with a thin abdominal wall. Inability to deeply inspire during deep palpation of the right upper quadrant is often observed (Murphy's sign). The presence of scleral icterus or frank jaundice makes the diagnosis of acute cholecystitis unlikely.

Importantly, approximately 90% of patients with gallstones are asymptomatic. Thus, patients with gallstones will present with abdominal pain that is not due to the gallstones, and consideration of alternative diagnoses needs to be maintained. There is no need for treatment of asymptomatic patients, regardless of other medical conditions.

A tabular or chart listing of features and signs and symptoms

Table I. Less typical clinical presentations of cholecystitis

1. Acalculous cholecystitis

Ischemic in origin, most typically observed as a complication of cardiopulmonary bypass or shock.

2. Chronic cholecystitis

Long-standing intermittent pain, typically exacerbated by meals. Most typically diagnosed by histological evidence of chronic inflammation in surgical specimens of patients with symptomatic cholelithiasis. Not due to acute occlusion of the cystic duct.

3. Hydropic gallbladder

Chronic occlusion of the cystic duct. The gallbladder is filled with clear, water-like fluid.

4. Mirizzi's syndrome

Chronic cholecystitis with retraction and fibrosis of gallbladder leading to hepatic duct occlusion, or due to a large stone in the cystic duct, causing compression of both cystic duct and common hepatic duct. Thus, patients present with obstructive jaundice.

5. Falsely positive ultrasound in the setting of cirrhosis.

Cirrhosis can lead to thickening of the gallbladder wall and ascites without occlusion of the cystic duct, infection, or symptoms.

Table II. Differential diagnoses

1. Cholangitis

Suspect with significant elevation of bilirubin (total bilirubin >3), rigors, signs of sepsis. Can rapidly progress to shock and death.

2. Pancreatitis

Epigastric pain through to the back. Nausea and vomiting. Amylase/lipase levels should be elevated.

3. Peptic ulcer disease

Epigastric pain radiating to the back. Pain relieved with eating but then recurs. May have melena or guaiac-positive stools.

4. Gastritis

Epigastric pain, vomiting, loss of appetite, and feeling of satiety after small meal. Can be chronic or acute in nature.

A pulsating mass may be palpated but is usually diagnosed with ultrasound or CT.

11. Mesenteric ischemia

Pathognomonic feature of abdominal pain out of proportion to the physical exam.

12. Myocardial infarction

May present with epigastric pain and can also have associated nausea and vomiting.

13. Right lower lobe pneumonia

Pain with respiration, cough. Lack of anorexia.

14. Pyelonephritis

Costovetebral tenderness greater than abdominal pain.

15. Symptomatic nephrolithiasis

Colic-type pain but location should be below right upper quadrant, more in the flank

16. Appendicitis or diverticulitis

May completely mimic symptoms and physical exam but are differentiated by imaging.

17. Fitz-Hugh-Curtis syndrome

Pelvic inflammatory disease presenting as right upper quadrant pain.

How can I confirm the diagnosis?

Laboratory studies

Blood work should include a complete blood count with differential liver function tests, serum amylase and/or lipase, and an abdominal ultrasound. A leukocytosis, or elevated percentage of premature white cells (bands) or neutrophils should be present. Pericholecystic hepatitis may lead to modest elevations in liver injury tests including the AST, ALT, alkaline phosphatase, and bilirubin.

Imaging

Right upper quadrant ultrasound (US). In addition to identifying gallstones, features of ultrasonic imaging known to correlate with acute cholecystitis include gallbladder wall thickening (0.4 cm or greater) and pericholecystic fluid. Positive results can be classified as uncomplicated versus complicated. (See Figure 1.)

Uncomplicated results include positive sonographic Murphy's sign, gallstone impacted in neck of gallbladder, or gallbladder wall thickening. Complicated results include fluid around the gallbladder or abscess, gas in the gallbladder wall or lumen without prior ERCP, or asymmetric wall thickening suggestive of malignancy. The presence or absence of intra- and extra-hepatic bile duct dilation is well assessed by US.

Hepatobiliary iminodiacetic acid (HIDA). A positive HIDA scan is highly specific for acute cholecystitis in the absence of severe liver dysfunction. Most patients with acute cholecystitis will not require a HIDA scan. The test consists of intravenous injection of technetium-labeled iminodiacetic acid that is taken up by the liver and excreted into the biliary tract. Nonvisualization of the gallbladder (within 4 hr) is diagnostic of cystic duct occlusion. (See Figure 2.) A CCK-HIDA has also been used as a diagnostic test gallbladder and biliary dyskinesia. In this setting, the gallbladder is visualized and radiotracer quantitated prior to and following the administration of CCK. Biliary dyskinesia is diagnosed if the majority of radiotracer remains in the gallbladder (typically <20% ejection fraction, although some authors advocate up to 40% ejection fraction as diagnostic).

Computerized tomography (CT). As up to 80% of gallstones are radiolucent, CT is not the diagnostic test of choice for biliary tract disease. However, it is appropriate to further evaluate ultrasound findings suggestive of possible malignancy or if the presenting symptoms place a diagnosis best evaluated by CT above biliary tract diagnoses (i.e., nephrolithiasis). Typical findings of acute cholecystitis include gallbladder distention and wall thickening, and pericholecystic inflammation.

What other diseases, conditions, or complications should I look for in patients with gallstones/cholecystitis?

Choledocholithiasis

Liver abscess

Intestinal fistula (colon or duodenum)

Gallbladder cancer

Pancreatitis

Steatotic hepatitis

Hemolysis

What is the right therapy for the patient with cholecystitis?

The right therapy is cholecystectomy.

What is the most effective initial therapy?

Early cholecystectomy is the most effective initial therapy.

Listing of usual initial therapeutic options, including guidelines for use, along with expected result of therapy.

Other approaches including lithotripsy, dissolution, and surgical extraction of gallstones without cholecystectomy have proven ineffective or even harmful.

A listing of a subset of second-line therapies, including guidelines for choosing and using these salvage therapies

1. Delayed cholecystectomy. In patients in whom cholecystitis presents late in the disease course, after approximately 4 days of inflammation, the risk of complications from cholecystectomy are markedly increased; thus, initial treatment should be intravenous antibiotics with a spectrum that covers enteric organisms. Cholecystectomy is performed 6 weeks later, or for clinical failure of antibiotic therapy to resolve symptoms.

2. Cholecystostomy. Image-guided drainage of the gallbladder is appropriate when the risk of cholecystectomy is prohibitive and there is clinical failure of antibiotic therapy.

Listing of these, including any guidelines for monitoring side effects.

N/A

How should I monitor the patient with cholecystitis?

After successful surgical management, three late complications need to be remembered and considered. These complications include:

1. Post-cholecystectomy or "bile salt" diarrhea. Typically, the patient complains of diarrhea ever since surgery. Clostridium difficile infection must also be considered. Treatment is empiric administration of cholestyramine for 6 months.

2. Biliary stricture. Thought to be the result of an ischemic event or thermal injury to the common bile duct. Can present up to 5 years after surgery.

3. Retained common bile duct stones. Presents within 2 years of surgery. Later presentation is attributed to primary common bile duct stones. Routine intraoperative cholangiography has revealed that approximately 10% of patients without biliary dilation or hyperbilirubinemia have stones within the common bile duct at time of cholecystectomy. Only 1% will develop symptoms; thus, 90% of these gallstones pass without incident.

If a post-cholecystectomy patient presents with jaundice or abnormal LFTs (alkaline phosphatase is the most sensitive marker), a CT scan may be of value to assess arterial anatomy and the status of the biliary tree, but most patients may proceed directly to ERCP for diagnosis and initial treatment of these complications.